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Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn.
J Comp Neurol. 2005 May 30; 486(2):169-78.JC

Abstract

Ionotropic glutamate receptors (IGR), including NMDA, AMPA, and kainate receptors, are expressed in terminals with varied morphology in the superficial laminae (I-III) of the dorsal horn of the spinal cord. Some of these terminals can be identified as endings of primary afferents, whereas others establish symmetric synapses, suggesting that they may be gamma-aminobutyric acid (GABA)-ergic. In the present study, we used confocal and electron microscopy of double immunostaining for GAD65, a marker for GABAergic terminals, and for subunits of IGRs to test directly whether IGRs are expressed in GABAergic terminals in laminae I-III of the dorsal horn. Although colocalization is hard to detect with confocal microscopy, electron microscopy reveals a substantial number of terminals immunoreactive for GAD65 also stained for IGRs. Among all GAD65-immunoreactive terminals counted, 37% express the NMDA receptor subunit NR1; 28% are immunopositive using an antibody for the GluR2/4 subunits of the AMPA receptor; and 20-35% are immunopositive using antibodies for the kainate receptor subunits GluR5, GluR6/7, KA1, or KA2. Terminals immunoreactive for IGR subunits and GAD65 establish symmetric synapses onto dendrites and perikarya and can be presynaptic to primary afferent terminals within both type 1 and type 2 synaptic glomeruli. Activation of presynaptic IGR may reduce neurotransmitter release. As autoreceptors in terminals of Adelta and C afferent fibers in laminae I-III, presynaptic IGRs may play a role in inhibiting nociception. As heteroreceptors in GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may have an opposite role and even contribute to central sensitization and hyperalgesia.

Authors+Show Affiliations

Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15844209

Citation

Lu, Chun-Rong, et al. "Ionotropic Glutamate Receptors Are Expressed in GABAergic Terminals in the Rat Superficial Dorsal Horn." The Journal of Comparative Neurology, vol. 486, no. 2, 2005, pp. 169-78.
Lu CR, Willcockson HH, Phend KD, et al. Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. J Comp Neurol. 2005;486(2):169-78.
Lu, C. R., Willcockson, H. H., Phend, K. D., Lucifora, S., Darstein, M., Valtschanoff, J. G., & Rustioni, A. (2005). Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. The Journal of Comparative Neurology, 486(2), 169-78.
Lu CR, et al. Ionotropic Glutamate Receptors Are Expressed in GABAergic Terminals in the Rat Superficial Dorsal Horn. J Comp Neurol. 2005 May 30;486(2):169-78. PubMed PMID: 15844209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. AU - Lu,Chun-Rong, AU - Willcockson,Helen H, AU - Phend,Kris D, AU - Lucifora,Simona, AU - Darstein,Melanie, AU - Valtschanoff,Juli G, AU - Rustioni,Aldo, PY - 2005/4/22/pubmed PY - 2005/7/29/medline PY - 2005/4/22/entrez SP - 169 EP - 78 JF - The Journal of comparative neurology JO - J. Comp. Neurol. VL - 486 IS - 2 N2 - Ionotropic glutamate receptors (IGR), including NMDA, AMPA, and kainate receptors, are expressed in terminals with varied morphology in the superficial laminae (I-III) of the dorsal horn of the spinal cord. Some of these terminals can be identified as endings of primary afferents, whereas others establish symmetric synapses, suggesting that they may be gamma-aminobutyric acid (GABA)-ergic. In the present study, we used confocal and electron microscopy of double immunostaining for GAD65, a marker for GABAergic terminals, and for subunits of IGRs to test directly whether IGRs are expressed in GABAergic terminals in laminae I-III of the dorsal horn. Although colocalization is hard to detect with confocal microscopy, electron microscopy reveals a substantial number of terminals immunoreactive for GAD65 also stained for IGRs. Among all GAD65-immunoreactive terminals counted, 37% express the NMDA receptor subunit NR1; 28% are immunopositive using an antibody for the GluR2/4 subunits of the AMPA receptor; and 20-35% are immunopositive using antibodies for the kainate receptor subunits GluR5, GluR6/7, KA1, or KA2. Terminals immunoreactive for IGR subunits and GAD65 establish symmetric synapses onto dendrites and perikarya and can be presynaptic to primary afferent terminals within both type 1 and type 2 synaptic glomeruli. Activation of presynaptic IGR may reduce neurotransmitter release. As autoreceptors in terminals of Adelta and C afferent fibers in laminae I-III, presynaptic IGRs may play a role in inhibiting nociception. As heteroreceptors in GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may have an opposite role and even contribute to central sensitization and hyperalgesia. SN - 0021-9967 UR - https://www.unboundmedicine.com/medline/citation/15844209/Ionotropic_glutamate_receptors_are_expressed_in_GABAergic_terminals_in_the_rat_superficial_dorsal_horn_ L2 - https://doi.org/10.1002/cne.20525 DB - PRIME DP - Unbound Medicine ER -